Chronic adolescent stress causes sustained impairment of cognitive flexibility and hippocampal synaptic strength in female rats.

Females that experience chronic stress during development, particularly adolescence, are the most vulnerable group to stress-induced disease. While considerable attention has been devoted to stress-induced manifestation of anxiety, depression, and PTSD, evidence indicates that a history of chronic stress is also a risk factor for cognitive decline and dementia - with females again in a higher risk group. This interplay between sex and stress history indicates specific mechanisms drive neural dysfunction across the lifespan. The presence of sex and stress steroid receptors in the hippocampus provides a point of influence for these variables to drive changes in cognitive function. Here, we used a rodent model of chronic adolescent stress (CAS) to determine the extent to which CAS modifies glutamatergic signaling resulting in cognitive dysfunction. Male and female Wistar rats born in-house remained non-stressed (NS), unmanipulated aside from standard cage cleaning, or were exposed to either physical restraint (60 min) or social defeat (CAS) each day (6 trials each), along with social isolation, throughout the adolescent period (PND 35-47). Cognition was assessed in adult (PND 80-130) male and female rats (n = 10-12) using the Barnes Maze task and the Attention Set-Shift task. Whole hippocampi were extracted from a second cohort of male and female rats (NS and CAS; n = 9-10) and processed for RNA sequencing. Brain tissue from the first cohort (n = 6) was processed for density of glutamatergic synaptic markers (GluA1, NMDA1a, and synaptophysin) or whole-cell patch clamping (n = 4) to determine glutamatergic activity in the hippocampus. Females with a history of chronic stress had shorter latencies to locate the goal box than NS controls during acquisition learning but showed an increased latency to locate the new goal box during reversal learning. This reversal deficit persisted across domains as females with a history of stress required more trials to reach criterion during the reversal phases of the Attention Set-Shift task compared to controls. Ovariectomy resulted in greater performance variability overall during reversal learning with CAS females showing worse performance. Males showed no effects of CAS history on learning or memory performance. Bioinformatic prediction using gene ontology categorization indicated that in females, postsynaptic membrane gene clusters, specifically genes related to glutamatergic synapse remodeling, were enriched with a history of stress. Structural analysis indicated that CAS did not alter glutamate receptor density in females. However, functionally, CAS females had a decreased AMPA/NMDA-dependent current ratio compared to controls indicating a weakening in synaptic strength in the hippocampus. Males showed only a slight change in density of NMDA1a labeling in the CA3 region with a history of stress. The data observed here suggest that females are at risk for impaired cognitive flexibility following a history of adolescent stress, possibly driven by changes in glutamatergic signaling.

[Program for the prevention and control of acute respiratory diseases in infancy in Santiago, Chile]. / Programa de prevención y control de las enfermedades respiratorias agudas de la infancia en Santiago, Chile.

This paper describes and examines the activities for the prevention and control of acute respiratory infections (ARI) carried out by a pediatric program in a government health service that provides care to a low-income population in Santiago, Chile. The study area has a population of just over one million people and is served by one general hospital, 16 primary care clinics, and eight rural health posts. Specific activities carried out by the ARI program include personnel training as well as control measures at the primary care level and hospitalization of children with severe ARI. In the first 5 years of the program (1990-1994), a reduction in annual mortality from pneumonia from 3.0 to 1.7 per 1,000 was observed among children under the age of one year, which contributed to a decline in infant mortality from 13.5 to 8.9 deaths per 1,000 live births. In 1994, program costs amounted to US$ 224,000. Judging from the results obtained, the ARI prevention and control program has made a valuable contribution in the area of child health.

Risk factors associated with inguinal hernias: a case control study.

OBJECTIVES: To assess reported risk factors for the development of inguinal hernias, to develop a method of quantifying physical effort, and to correlate them. DESIGN: Case control study. SETTING: District hospital, Valencia, Spain. SUBJECTS: 290 selected patients who had undergone inguinal hernia repair, and 290 age and sex matched controls. INTERVENTIONS: Each patient was interviewed and data collected on a specially designed questionnaire, and an "effort score" calculated. MAIN OUTCOME MEASURES: Incidence of specified risk factors. RESULTS: The only significant risk factor was physical effort (lifting heavy objects repeatedly over long periods of time), relative risk 2.92, 95% confidence interval 2.11 to 4.04. In addition, there were significant differences between index cases and controls in standard of education (p < 0.001), consumption of alcohol (p = 0.02), chronic cough (p < 0.001), net monthly income (p = 0.04), and amount of physical effort expended (p < 0.001). Patients with indirect hernias expended significantly more physical effort and were both heavier and taller, and patients with femoral hernias waited significantly longer than the others before having their hernias repaired. CONCLUSION: Inguinal hernias are associated with the expenditure of a considerable amount of physical effort, and are commoner among younger, poorly educated manual workers.